The goal of this proposal is to obtain a state-of-the-art Nikon A1R Enhanced Resolution (ER) inverted confocal microscope to replace a heavily used and obsolescent 13-year-old Zeiss 510 META confocal microscope in the Microscopy Imaging Center (MIC) in the Larner College of Medicine at the University of Vermont. This instrument would meet the increasing demand for advanced features not supported by the existing thirteen- year-old microscope and would sustain the need for efficient confocal imaging for years to come with a reliable, high performance system. Importantly, this microscope will permit extended live cell and tissue imaging for short- and long-term physiological experiments. The requested Nikon A1R-ER confocal microscope, with its sub-diffraction limited resolution will be essential for future cutting edge biomedical research for the Larner College of Medicine community, as well as the University of Vermont generally. The rationale for a new instrument is to replace an obsolescent Zeiss 510 META for which an annual preventative maintenance agreement is no longer offered by Zeiss, and sustain our current confocal imaging capabilities with a broader range of sophisticated imaging applications. A state-of-the- art point scanning confocal system will also meet the progressively increasing demand for specialized confocal imaging, especially for investigations using live cells and thick tissues, FRET/FRAP analyses, and simultaneous multi-channel imaging. Eight investigators have been identified as Major Users for the purpose of this application because they represent most of the projected demand for the requested instrument given their existing and proposed applications requirements. We have also identified a strong minor user group that will occupy the remaining time on the proposed new system. The Major User and Minor User groups assembled for this proposal represent faculty and biomedical research interests from the Departments of Biochemistry, Medicine, Microbiology & Molecular Genetics, Molecular Physiology & Biophysics, Neuroscience, Pathology & Laboratory Medicine, and Pharmacology. Moreover, these faculty also represent the Vermont Cancer Center, the Cardiovascular Research Institute, the Vermont Lung Biology Center, the Vermont Center for Immunology and Infectious Diseases, and the Cellular, Molecular, and Biomedical Sciences Graduate Program. The addition of a new inverted confocal microscope to the MIC is expected to significantly absorb the progressively expanding numbers of users of the facility and meet their specific technical requirements. It will also afford the capacity for advanced high-quality imaging capabilities and ensure sustained and efficient use for the UVM biomedical research community for the future.